PROSITE documentation PDOC51802
Zinc finger CCHHC-type profile


Zinc finger (ZF) proteins are a large family of metalloproteins that utilize zinc for structural purposes. Zinc coordinates to a combination of cysteine thiol and histidine imidazole residues within the ZF polypetide sequence resulting in a folded and functional protein. The CCHHC family of ZFs is a small family of "nonclassical" ZFs that are essential for the development of the central nervous system. These proteins have up to seven putative zinc-binding sequences, usually arranged in sets of two or more sequences. The CCHHC-type zinc finger is able to bind specific double-stranded DNA sequences [1,2,3,4,5].

The CCHHC-type zinc finger contains five absolutely conserved cysteine and histidine residues (rather than the more usual four) with the sequence C-P-x-P-G-C-x-G-x-G-H-x(7)-H-R-x(4)-C. The second histidine has been shown to coordinate Zn(II) along with the three cysteines residues. The first His plays a different role in stabilizing the structure, stacking between the metal-binding core and an aromatic residue that is relatively conserved within this domain family. CCHHC-type zinc fingers form small compact structures that can sit entirely within the major groove of DNA (see <PDB:2JX1>) [1,2,3,4,5].

Some proteins known to contain a CCHHC-type zinc finger are listed below:

  • Animal myelin transcription factor 1 (MyT1), or neural zinc finger 2 (NZF2), a transcription factor that contains seven copies of the CCHHC-type zinc finger. It binds to sites in the proteolipid protein promoter.
  • Vertebrate MyT1-like (MyT1L/NZF1), appears to be involved in neural development.
  • Vertebrate Suppressor of Tumorigenicity 18 (ST18/NZF3), a breast cancer tumor suppressor.
  • Vertebrate L3MBTL, a member of the Polycomb group of proteins, which function as transcriptional repressors in large protein complexes.
  • Vertebrate L3MBTL3, a possible tumor suppressor.
  • Vertebrate L3MBTL4.

The profile we developed covers the entire CCHHC-type zinc finger.

Last update:

June 2016 / First entry.


Technical section

PROSITE method (with tools and information) covered by this documentation:

ZF_CCHHC, PS51802; Zinc finger CCHHC-type profile  (MATRIX)


1AuthorsGamsjaeger R. Swanton M.K. Kobus F.J. Lehtomaki E. Lowry J.A. Kwan A.H. Matthews J.M. Mackay J.P.
TitleStructural and biophysical analysis of the DNA binding properties of myelin transcription factor 1.
SourceJ. Biol. Chem. 283:5158-5167(2008).
PubMed ID18073212

2AuthorsGamsjaeger R. O'Connell M.R. Cubeddu L. Shepherd N.E. Lowry J.A. Kwan A.H. Vandevenne M. Swanton M.K. Matthews J.M. Mackay J.P.
TitleA structural analysis of DNA binding by myelin transcription factor 1 double zinc fingers.
SourceJ. Biol. Chem. 288:35180-35191(2013).
PubMed ID24097990

3AuthorsLee S.J. Michel S.L.J.
TitleStructural metal sites in nonclassical zinc finger proteins involved in transcriptional and translational regulation.
SourceAcc. Chem. Res. 47:2643-2650(2014).
PubMed ID25098749

4AuthorsBesold A.N. Michel S.L.
TitleNeural Zinc Finger Factor/Myelin Transcription Factor Proteins: Metal Binding, Fold, and Function.
SourceBiochemistry 54:4443-4452(2015).
PubMed ID26158299

5AuthorsBerkovits-Cymet H.J. Amann B.T. Berg J.M.
TitleSolution structure of a CCHHC domain of neural zinc finger factor-1 and its implications for DNA binding.
SourceBiochemistry 43:898-903(2004).
PubMed ID14744132

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